PARP-14 Binds Specific DNA Sequences to Promote Th2 Cell Gene Expression

Abstract

PARP-14, a member of the poly ADP-ribose polymerase super family, promotes T helper cell 2 (Th2) differentiation by regulating interleukin-4 (IL-4) and STAT6-dependent transcription. Yet, whether PARP-14 globally impacts gene regulation has not been determined. In this report, using an RNA pol II ChIP-seq approach, we identify genes in Th2 cells that are regulated by PARP-14, and either dependent or independent of ADP-ribosyltransferase catalytic activity. Our data demonstrate that PARP-14 enhances the expression of Th2 genes as it represses the expression of Th1-associated genes. Among the relevant targets are Signal Transducer and Activator of Transcription genes required for polarizing Th1 and Th2 cells. To define a mechanism for PARP-14 function, we use an informatics approach to identify putative PARP-14 DNA binding sites. Two putative PARP-14 binding motifs are identified in multiple Th2 cytokine genes, and we demonstrate that PARP-14 interacts with each motif using in vitro binding assays. Taken together our results indicate that PARP-14 is an important factor for T helper cell differentiation and it binds to specific DNA sequences to mediate its function.

Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine

“…This group included genes on immune cells such as C4b, Cd83 an important activation marker on B-cell, T-cell, and dendritic cell populations44, Fcgr3 , Ighm, Irf9 , Ly6e , and Parp14 . PARP-14 promotes Th2 and Th17 cell formation and steers the antibody subclass distribution4546.…”

The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression

“…PARP12, which has high sequence similarity to PARP13 (ZAP), has previously been shown to block both cellular and viral protein translation and inhibit virus replication by both ADP-ribosylation dependent and independent mechanisms [30]. On the other hand, PARP14 was not previously shown to inhibit virus replication but rather was shown to modulate both innate and adaptive immune responses [15,63,68,71]. Both proteins are known components of stress granules where they interact with a variety of proteins, including Argonaute 2 and PARP13 (ZAP) [16].…”

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

“…The IFNγ and IL-4 mechanisms appear distinct, but they may be partial and complementary pictures of a complex biology. regulating STAT6-dependent Gata3 expression and that PARP14-deficient mice show reduced symptoms of allergic airway disease Riley et al 2013). PARP14 enhances STAT3-dependent Th17 differentiation (Mehrotra et al 2015).…”